Coucke et al. (2003) localized the arterial tortuosity syndrome locus to 20q13 by homozygosity mapping. Three years later, Coucke et al. narrowed the candidate region on chromosome 20q13.1 to a 1.2-Mb region containing seven genes. Mutations in one of these genes, SLC2A10, were identified in six ATS families. In two families originating from the same region in Morocco, Coucke et al. (2006) found that arterial tortuosity syndrome was associated with a homozygous nonsense mutation, 510G-A (W170X) in the SLC2A10 gene. In an additional family, Coucke et al. (2006) found a homozygosity for a frameshift mutation, 961delG (V321fsX391). Deficiency of the facilitative glucose transporter GLUT10, which is encoded by SLC2A10, is associated with upregulation of the TGF-beta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The findings of Coucke et al. (2006) could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggested that therapeutic compounds intervening with TGF-beta signaling represent a new treatment strategy.

Faiyaz-Ul-Haque et al. (2008) carried out a molecular study on 14 out of 15 patients and 28 unaffected individuals from 10 apparently unrelated consanguineous families from Qatar. Eight of the families belonged to a large consanguineous kindred that was part of an extended Bedouin tribe originally reported by Abdul Wahab et al., 2003. Recombination events between D20S96 and D20S86 and between D20S886 and D20S178 defined the centromeric and telomeric boundaries to a 2.7 Mbp region on 20q13.1. The mapped haplotypes were found to be segregated with the diseases in all affected individuals. The defined region contains the SCL2A10 gene. DNA sequencing of this candidate gene was performed and detected a homozygous c.243C-to-G mutation in the 14 affected patients. This mutation encodes a p.Ser81Arg substitution in the third transmembrane domain of the facilitative glucose transporter, GLUT10 protein. Unaffected carrier parents were found to be heterozygous for this mutation. This mutation was not found in non-carrier individuals without clinical features of ATS. Identification of this recurrent mutation as well as shared haplotypes in 14 patients in 10 families from Qatar, led Faiyaz-Ul-Haque et al. (2008) to strongly suggest that the c.243C-to-G mutation in families from the region may have a common origin and shared ancestry.

Faiyaz-Ul-Haque et al. (2009) reported a novel and a known mutation in the SLC2A10 gene in two unrelated Saudi families affected with Arterial Tortuosity Syndrome. The first of these families had one affected child, and sequencing of his SLC2A10 gene revealed the presence of a novel c.313C>T (p.Arg105Cys) homozygous missense mutation. The substitution occurred in the second extracellular domain of the GLUT10 protein at a residue that sequence alignment showed to be evolutionarily conserved across species. PolyPhen program predicted this to be a 'Probably Damaging' mutation. The consanguineous parents were found to be homozygous carriers of this mutation. This mutation was not found in 256 control Arab chromosomes. The six affected patients in two sibships in the second family were all found to carry two copies of a previously reported c.243C>G (p.Ser81Arg) missesnse mutation in the SLC2A10 gene, affecting the third transmembrane domain of the protein. All the three parents that were tested were found to be heterozygous carriers of this mutation.